Effective radiotherapy is based on the selective killing of tumor cells which, however, are often hypoxic and, therefore, have increased radioresistance. There are compounds which, when present during irradiation, increase cell sensitivity to killing by mechanism(s) not well understood. It is the objective of the proposed research to characterize the effects of hypoxic-cell radiosensitizers on the formation and repair of radiation-induced damage in DNA of mammalian cells. Several different compounds will be studied with Chinese hamster ovary cells in suspension. Specifically, the effect of sensitizers on the yield and subsequent repair of (1) base damage of the 5,6-dihydroxy-dihydrothymine type and (2) single- and double-strand breaks under aerobic and hypoxic conditions of irradiation will be measured. Thymine base damage is assayed by chemical degradation of the modified base in DNA and strand breaks by elution of DNA from filters at neutral and alkaline pH.